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Dermatomyositis/Polymyositis
Irina Alexandrovna Zborovskaya – doctor of medical sciences, professor,cathedral professor of hospital therapy with the course of clinical rheumatology of the doctors improvement faculty of Volgograd state medical university, director of the Federal Budgetary State Institution (FBSI) “Research and development institute of clinical and experimental rheumatology” of the RAMS, head of the regional Osteoporosis Center, presidium member of the Association of rheumatologists of Russia, member of the editorial boards of the magazines “Scientific and practical rheumatology” and “Modern rheumatology”
Definition. Dermatomyositis (DM) is a disease characterised by systemic involvement of striated muscles and characteristic dermatologic manifestations. It belongs to the group of systemic diseases of the connective tissue. If skin is not involved, the term “polymyositis” (PM) is typically used.
Epidemiology. DM can occur in people of any age. The incidence of dermatomyositis has been estimated 5 cases per million people every year. DM affects women more frequently than men (3:1 ratio); DM with an associated malignancy affects men as frequently as women (1:1 ratio); DM with characteristic connective tissue findings affects women ten times as frequently as men (10:1 ratio); inclusion body myositis (IBM) affects men 3 times as frequently as women. Two peak ages of onset exist. In adults, the peak age of onset is approximately 35 – 60 years, and, in children, the peak age is approximately 11 – 17 years. Polymyositis in adults is often associated with a malignancy. Polymyositis with an associated malignancy amounts to 20 – 30% of all cases. It usually affects adults older than 50.
Aetiology and pathogenesis. Aetiology remains unknown. Dermatomyositis and polymyositis as well as some other diseases are often referred to as “idiopathic inflammatory myopathies” as they are usually associated with characteristic muscular findings.
Viral aetiology and the effect of some infectious agents should be also considered. Some cases of dermatomyositis and polymyositis after rubella, herpes infection, administration of vaccines and sera as well as some drugs have been reported. Exposure to cold, insolation, increased physical activity have been suggested as possible triggers of the disease. High-titred antibodies to picornaviruses are typically revealed in blood of children with DM. High – titred antibodies to Toxoplasma gondii species are found in blood of adults with PM. However, the attempts to obtain viruses from the muscles of patients and to reproduce myositis in experimental animals by means of administering the extracts of muscular tissue of the sick were unsuccessful. Thus, the role of infectious agents, including viruses in pathogenesis of DM is uncertain.
Nevertheless, we should consider that the formation of autoantibodies to cytoplasmic proteins is associated with immune reactions to changed viruses whose antigens are the same as those of the body.
A genetic predisposition may also exist. Cases of DM in first-degree relatives have been reported. It may be linked to certain human leukocyte antigen HLA types (for example, B8, DR3, DRW52).
In most patients with inflammatory myopathies autoantibodies to nuclear antigens (ANA) may be present. Circulating immune complexes form in tissues, muscles, skin and vessels resulting in immune complex inflammation. The development of DM associated with a malignancy may be caused either by a direct toxic effect of tumorous agents on the muscles or by the development of autoimmune reactions due to the link between tumour-specific and muscular tissue antigens.
There is evidence for the role of cellular immune disturbances in the development of DM and PM. It has been suggested that muscles are involved in PM due to increased T-cell cytokine toxicity. These cytokines induce aberrant expression of major histocompatibility complex (MHC) class I molecules on muscle cells. Destruction of muscle fibres and their infiltration by sensitized lymphocytes and macrophages usually occur. PM is caused by the direct effect of lymophotoxins produced by lymphocytes on muscle fibers (perforin and granzim).
Pathomorphology. Striated musculature is most commonly affected. Myocardium and skin are involved less commonly. Lymphocytes and plasmatic cells usually prevail in inflammatory infiltrates. Macrophages, eosinophils and neutrophils may be also present. In PM CD8+ cells infiltrate muscle fibers, while in DM CD4+ cells and B-lymphocytes accumulate in the area of small vessels.
Muscle involvement is manifested by focal necrosis, destruction of muscle fibers and loss of transverse striation.
Signs of regeneration of skeletal muscles are manifested by increased amounts of muscular nuclei as well as basophilia of muscle fibers. In chronic DM interstitial fibrous infiltrates often occur.
In a prolonged course of DM muscular atrophy resulting in the formation of dense connective tissue is often observed. Irreversible fibrous contractures typically develop.
Skin involvement is manifested by atrophy of papillae, thinning-out of the epidermis, thickening and structural changes of collagen fibers.
Classification:
- Primary PM
- Primary DM
- DM or PM associated with malignancy
- Juvenile DM or PM
- PM or DM associated with another connective-tissue diseases